Steroid esters and a process for their preparation

ABSTRACT

NOVEL ESTERS OF STERIODS HAVING THE FORMULA   (R1-SO2-O)NA   WHEREIN A IS AN N-VALENT STEROID, R1 IS ALKYL HAVING AT LEAST 2 CARBON ATOMS, CYCLOALKYL, ARALKYL, ALKOXY, CYCLOALKOXY, AROXY, ARALKOXY, ALKARYLOXY, N,N-DIALKYLAMINO, N-ALKYL-N-CYCLOALKYL, AMINO, N-ACYL-N-ARYL AMINO OR POLYMETHYLENEIMINO AND N IS 1 OR 2, PREPARED BY REACTING AN ACID HALIDE OF THE FORMULA R1-SO2-X, WHEREIN X IS FLOURINE, CHLORINE, BROMINE, OR IODINE WITH A STEROID COMPOUND HAVING THE FORMULA A(OH)N WHERE A AND N ARE AS DEFINED ABOVE. THE NEW ESTERS ARE CHARACTERIZED BY IMPROVED ANDROGENIC, ANABOLIC, GESTATIONAL AND ESTROGENIC ACTIVITIES.

United States Patent Office 3,806,503 Patented Apr. 23, 1974 STEROIDESTERS AND A PROCESS FOR THEIR PREPARATION Sigfrid Schwarz, Jena,Germany, assignor to VEB Jenapharm, Jena, Germany N Drawing. Filed Nov.12, 1969, Ser. No. 876,095 Int. Cl. C07c 169/08, 173/10 US. Cl. 260-239521 Claims ABSTRACT OF THE DISCLOSURE Novel esters of steroids having theformula BACKGROUND OF THE INVENTION The present invention relates to newsteroid esters and to a method for their preparation.

Steroid compositions have been made with at least one group of theformula R -SO --O wherein R was methyl, phenyl or substituted phenyl.

It is known in the art to prepare such steroid compounds having at leastone group corresponding to Rz-SOr-O by reacting an acid chloride of theformula R SO Cl with a steroid alcohol or phenol in the presence ofpyridine. However, the reaction does not, or substantially does not takeplace if an acid chloride of the formula R SO --Cl in which R is alkylhaving at least 2 carbon atoms, cycloalkyl, aralkyl, alkoxy,cycloalkoxy, aroxy, aralkoxy, alkaryloxy, N,N-dialkylamino, N-alkyl-N-cycloalkylamino, N-acyl-N-arylamino or polymethyleneimino, are used inthe reaction with the steroid alcohol or phenol in the presence ofpyridine. This is also true even if a high molar excess of acid chlorideand/or pyridine and extremely long reaction times and/or high reactiontemperatures are applied.

An object of the invention is therefore to provide new steroid estershaving at least one R SO O group which are therapeutically useful andwhich are characterized by their prolonged depot action.

Another object of the invention is to provide a process for thepreparation of new steroid esters having at least one R SO O-- groupwhich are therapeutically useful and which are characterized by theirprolonged depot action.

A further object of this invention is to provide a simple and economicalmethod for the preparation of the new steroid esters.

The invention concerns steroid esters of the formula (R SO -O),,A,wherein A is an n-valent steroid radical, R is alkyl having at least 2carbon atoms, cycloalkyl, aralkyl, alkoxy, cycloalkoxy, aroxy, arakoxy,alkaryloxy, N,N-dialkylamino, N-alkyl-N-cycloalkyl amino,N-acyl-N-arylamino, or polymethyleneimino, and n is 1 or 2.

The steroid esters of the invention can be prepared by reacting an acidhalide of the formula R -SO --X wherein R has the above-identifiedmeaning and X is a member selected from the group consisting offluorine, chlorine, bromine and iodine, with a compound of the formulaA(()H) wherein A and n have the abovedesignated meanings.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferably, the process of theinvention is carried out in the presence of a sterically hindered amine.The presence of a sterically hindered amine generally allows forquantitative yields of the steroid esters of the invention.

Any suitable acid halide of the formula R SO -X in which R and X havethe above-identified meanings can be used according to the invention.Acid chlorides are preferred. Any suitable compound of the formula A(OH)in which A and n have the above-identified meanings is useful asstarting material. The following compounds are given as examples ofsuitable starting materials: C2H5SO2F, C H -SO CI,

(CH -NSO Br, compounds which are derived from cholestane, pregnane,androstane and estrane.

Any suitable esterically hindered amine can be used according to the theinvention, such as for example 2,6-dimethyl pyridine, 2,4,6 trimethylpyridine, triethylamine, triisopropylamine, bis trimethyl silyl amine,etc. It is preferred to carry out the reaction in an inert solvent, asfor example a hydrocarbon, i.e., benzene, a halogenated hydrocarbon,i.e., chlorobenzene, and trichloroethylene, an ester, i.e., acetic acidethyl ester, a ketone, i.e. acetone.

The steroid esters of the invention are new and can only be obtained bythe process of the invention, generally in quantitative yields. Theyhave valuable pharmacological properties and have been found to possessandrogenic, anabolic, gestational or estrogenic activity, which activityis maintained over prolonged periods following a single application.This depot effect is of particular significance for the application ofthe compounds of the invention in long-term therapy.

The following examples describe the manner and process of making andusing the invention but are not to be construed as limiting the same.

EXAMPLE 1 17a-ethinyl-3-(propane-Z-sulfonyloxy)-17fi-hydroxy- 1,3,5l0)estratriene l g. 17a ethinyl 3 hydroxy 17,8 trimethylsilyloxy-1,3,5(10)-estratriene was dissolved in 28 ml. of a mixture ofbenzene and triethylamine and to this solution 1.22 ml. propane 2sulfonyl chloride were added under stirring at room temperature. Thereaction mixture was kept for 2 hours at room temperature and thenpoured onto ice. After decomposition of excess acid chloride, thesolution was extracted with ether. The combined extracts were washedwith water until neutrality, dried over sodium sulfate and the solventthereafter removed. In order to decolorize the resulting residue, it wasdissolved in a small amount of benzene, filtered through a thin layer ofaluminum oxide (neutral, activity degree I) and the benzene removed invacuo. A colorless crystalline crude product was obtained which wasrecrystallized from acetone/ n-hexane. 2.1 g. 170: ethinyl 3(propane-2-sulfonyloxy) 17,8 trimethyl silyloxy 1,3,5(10)estratrienewere obtained. M.P. 127-129 G; [:1 1:0" (c.=1.0; dioxane).

1.10 g. 170: ethinyl 3 (propane 2 sulfonyloxy)- 1713 trimethyl silyloxy1,3,5(10)estratriene were dissolved at room temperature in 110 ml.hydrochloric acid containing methanol. The solution was kept for 15minutes at room temperature. It was then neutralized with a sodiumbicarbonate solution and thereafter concentrated in vacuo. The separatedprecipitate was collected by suction filtration, washed until neutralwith water, dried by standing and recrystallized from acetone/n-hexane.

0.88 g. 1711 ethyinyl 3 (propane-2-sulfonyloxy)- 176 hydroxy 1,3,5estratriene were thereby obtained. M.P. 160-161 C.; [a] +3.5 (c. =1.0;chloroform); vmax, 3615, 3315, 1610, 1500 (1350), 1365 cm.- (chloroform)EXAMPLE 2 17 a-ethinyl-3-(butane-1-sulfonyloxy)-17fl-hydroxy-1,3,5(10)-estratriene 1 g. of 170: ethinyl 3 hydroxy 17,3trimethylsilyloxy-1,3,5(10)-estratriene was dissolved in 27.4 ml. of amixture of benzene and 2,4,6-trimethylpyridine and with stirring 1.40ml. of butane-l-sulfonyl-chloride were added thereto at roomtemperature. The reaction mixture was kept for 2 hours at roomtemperature and then poured onto ice. After decomposition of the excessacid chloride, the solution was extracted with ether, washed untilneutral with water, dried over sodium sulfate and concentrated in vacuo.In order to decolorize the residue, it was dissolved in a small amountof benzene and filtered through a thin layer of aluminum oxide (neutral,activity degree I). The benzene was removed in vacuo. A colorless,crystalline crude 17oz ethinyl 3 (butane-l-sulfonyloxy) 17p trimethylsi1yloxy-l,3,5 10)-estratriene was obtained. 0.912 g. of this crudeproduct was dissolved at room temperature in 92 ml. of hydrochloric acidcontaining methanol. The solution was allowed to stand for minutes atroom temperature. After this, it was neutralized with a 5% hydrogencarbonate solution and concentrated in vacuo. 0.9 g. of an oilynon-crystallizable 17aethinyl 3 (butane 1 sulfonyloxy) 17 8 hydroxy-1,3,5(10)estratriene were obtained. u 3615, 3315, 1610, 1500, 1375 cm.-(chloroform).

EXAMPLE 3 17a-ethiny1-3- (octane-l-sulfonyloxy) -17,B-hydroxy- 1,3,5 10)-estratriene tral, activity degree I). 1.2 g. of an oily 17a ethinyl-3-(octane 1 sulfonyloxy) 17,3 hydroxy-1,3,5(10)- estratriene were therebyobtained which did not crystallize. 1 3610, 3315, 1610, 1585, 1500, 1375cm.- (chloroform).

4 EXAMPLE 4 1713- (ethane-sulfonyloxy) -4-estrene-3-one According to theprocedure of Example 1, from 1 g. 19-nortestosterone, 32 ml. benzene and6.9 m1. of a mixture of triethylamine and ethane sulfonylchloride,crystalline 17fl-(ethane-sulfonyloxy) 4 estrene-S-one was obtained. M.P.-132 C.; [041 +38 (CHCl u 1670, 1625, 1355, 1335, 1170 cm.- (CHClEXAMPLE 5 4-chloro-17B- (pentane-l-sulfonyloxy) -4- androstene-3-oneAccording to the procedure of Example 1, starting from 1 g. of4-chlorotestosterone, 27 ml. of benzene and 13.1 ml. of a mixture oftriethylamine and pentane-l-sulfonyl chloride, non-crystalliza'ble4-chloro 17p (pentane-lsulfonyloxy) 4 androstene-B-one was obtained. [a]2 +86 (CHCl v 1694, 1585, 1355, 1340, 1165 cm. (CHCla).

EXAMPLE 6 3 {3- ethane-sulfonyloxy -5 -cholestene According to theprocedure of Example 1, starting from 1 g. chloresterine, 48 ml.benzene, and 7.35 ml. of a mixture of triethylamine and ethanesulfonylchloride, 3,8 (ethane-sulfonyloxy) 5 cholestene was obtained.M.P. 131-133 C.; [a] 37 (CHC1 );1 1357, 1340, 1167 cm." (CHCl EXAMPLE 717a-ethinyl-3- (ethane-sulfonyloxy) -17,B-hydroxy- 1,3,5(10)-estratrieneThe process in this and the following examples was the same as inExample 1. Only the starting compounds were changed, as well as theiramounts. Accordingly, from 1 g. of 17m-ethinyl 3 hydroxytrimethylsilyloxy- 1,3,5(10)-estratriene, a mixture of 28 ml. benzeneand triethylamine and 1.03 ml. ethane-sulfonylchloride there wasobtained a crystalline l7a-ethinyl 3 (ethane-sulfonyloxy) 17,6 hydroxy1,3,5 (10) estratriene. M.P. 137-139 C.; [od z +3.5 (CHCl 11 3615, 3315,1605, 1495, 1370 cm. (CHCl EXAMPLE 8 17a-ethinyl-3-(propane-l-sulfonyloxy) -17p-hydroxy- 1,3,5 10)-estratriene17u-ethinyl-3-(propane-2-sulfonyloxy)-17fl-acetoxy- 1,3,5 l 0-estratriene The process was the same as in Example 1. The startingproducts were 0.92 g. 17a-ethinyl 3 hydroxy 17B- acetoxy 1,3,5(l0)estratriene, a mixture of 28 ml. benzene and triethylamine, and 1.22 ml.propane-2-sul fonylchloride. The final compound was a crystalline17aethinyl 3 (propane 2 sulfonyloxy) 17B acetoxy- 1,3,5(10) estratriene.M.P. 131133 C.; [why :0 (CHCl v g 3320, 1745, 1610, 1590, 1500, 1370',1350, 127.5, 11.90 cm. (CHCI 5 EXAMPLE 10 17a-ethinyl-3-(propane-2-sulfony1oxy)-17 p-valerianoxy- 1,3,5(10)-estratriene The process was the same as in Example 1. The startingproducts were 1.035 g. of 17a-ethinyl 3 hydroxy-17 8- valerianoxy1,3,5(10) estratriene, a mixture comprising 28 ml. benzene andtriethylamine and 1.22 ml. propane- 2-sulfonylchloride. The finalproduct obtained was 17aethyl 3 (propane 2 sulfonyloxy) 17,8valerianoxy- 1,3,5(10) estratriene. [a] +15.3 (CHCI 1 3320, 1755, 1615,1585, 1500, 1370, 1355, 1190 cm.- (CHCl EXAMPLE 11 17 a-chloroethinyl-3-propane-2-sulfonyloxy)- 17,3- hydroxy-1,3,5( 10) -estratriene Thestarting products were 1.09 g. 17a-chloroethinyl- 3 hydroxy 17ptrimethylsily1oxy-1,3,5 10)-estratriene, 28 ml. of a mixture of benzeneand triethylamine and 1.22 ml. propane-Z-sulfonyl bromide. There wasobtained a crystalline 17a chloroethinyl 3 (propane 2 sulfonyloxy) 17,8hydroxy 1,3,5(10) estratriene. M.P. 153-155 C.; v 3620, 2230, 1615,1590, 1500, 1370, 1355, 1190 cmr (CHCl EXAMPLE 123-(propane-Z-sulfonyloxy)-1,3,5 (10)-estratriene-17-one The startingproducts were 1 g. of estrone, a mixture amounting to 31 ml. comprisingtriethylamine and nitromethane, and 2.1 ml. propane-Z-sulfonylchloride.By the process described in Example 1, there was obtained a crystalline3-( propane 2 sulfonyloxy)-1,3,5(10)-estratriene- 17-one. M.P. 189-191C.; [(11 +118.5 (CHCl v 1745, 1615, 1590, 1500, 1370, 1355, 1190 cm.-(CHCI EXAMPLE 13 3- (propane-Z-sulfonyloxy) l 7,8-valerianoxy- 1,3,5 l-estratriene The process was again the same as in Example 1. Thestarting products 1 g. of 3-hydroxy-l7B-valerianoxy-1,3,5(10)-estratriene, 27.8 ml. of a mixture of benzene andtriethylamine and 1.5 ml. propane-Z-sulfonyl chloride. The final productobtained was a crystalline 3-(propane- 2-sulfony1oxy 17,6 valerianoxy1,3,5(10) estratriene. M.P. 102-103 0.; +31 (CHCI 11 1733, 1615, 1590,1500, 1370, 1355, 1185 cm. (CHCI EXAMPLE 14 313-(propane-Z-sulfonyloxy)--pregnene-20-one The process was the same as inExample 1. The starting products were 1.7 g. ofBfi-hydroxy-S-pregnene-20-one, 62.6 ml. of a mixture of benzene andtriethylamine and 3.02 ml. propane-2-sulfonylchloride. The final productwas a crystalline 3B-(propane-2-sulfonyloxy)-5-pregnene- 20-one. M.P.140-142" c.; M +217" 0110, 1700, 1355, 1335, 1180 cutc110,

EXAMPLE 1s Prednisone-21-( propane-Z-sulfonate) The process was the sameas in Example 1. The starting products were 1 g. of prednisone, 57 ml.of a mixture of nitromethane and triethylamine and 3 ml. propane-2-sulfonyl chloride. There was obtained as final product a crystallineprednisone-21-(propane-Z-sulfonate). M.P. 195-198 C.; [11], +170 (CHCl u3310, 1745, 1720, 1665, 1625, 1610, 1355, 1190 cm.- (KBr).

EXAMPLE 16 17a-ethinyl-3- (butane-Z-sulfonyloxy) -17;3-hydroxy- 1,3 ,5(-estratriene The process was the same as in Example 1. The startingproducts were 1 g. of17a-ethinyl-3-hydroxy-17fi-trimethylsilyloxy-l,3,5(10)-estratriene, 28ml. of a mixture of benzene and triethylamine and 1.75 ml.butane-Z-sulfonyl bromide. As final product there was obtained acrystalline 17a-ethinyl-3-(butane 2 sulfonyloxy)-17fi-hydroxy-l,3,5(10)-estratriene. M.P. 109-115 C.; [a] I 10 (CHCI v 3615, 3320, 1610,1590, 1500, 1370, 1185 cm. (CHCl EXAMPLE 17 17a-ethinyl-3-Z-methyl-propane-l-sulfonyloxy) 17fl-hydr0xy-1,3,5 10) -estratriene Theprocess was the same as in Example 1. The starting products were 1 g. of17a-ethinyl-3-hydroxy-17;3-trimethylsilyloxy-1,3,5(10)-estratriene, 28ml. of a mixture of benzene and triethylamine and 1.75 ml.2-methyl-propanel-sulfonylchloride. As final product there was obtaineda crystalline 17ot-ethinyl-3-(Z-methyl-propane-l-sulfonyloxy)-173-hydroxy-1,3,5(10)-estratriene. M.P. 9295 CL; [a] +3 (CHCI v 3615,3320, 1610, 1585, 1500, 1375, 1180 cmr (CHCl EXAMPLE 18 17a-ethinyl-3-(pentane-l-sulfonyloxy)-17B-hydroxy- 1,3,5(10)-estratriene The processwas the same as in Example 1. The starting products were 1 g. of17a-ethinyl-3-hydroxy-17fl-trimethylsilyloxyl,3,5(10)-estratriene, 28ml. of a mixture of benzene and triethylamine and 1.57 ml.pentane-1-sulfonylbromide. There was obtained an oily, non-crystalline17u-ethinyl 3 (pentane 1 sulfonyloxy)-17,3-hydroxy-1,3,5(10)-estratriene. [cc] +2.5 (CHCI 1 3615, 3320, 1615, 1590, 1500,1380, 1180 cm." (CHCI EXAMPLE 1917ot-ethinyl-3-(pentane-3-sulfonyloxy)-17,6-hydroxy-1,3,5(10)-estratriene In this example the same method was used as inExample 1. From 1 g. of17m-ethinyl-3-hydroxy-17fl-trimethy1sily1oxy-1,3,5(10)-estratriene, 28ml. of a mixture of benzene and triethylamine and 2.0 ml.pentane-3-sulfonylchloride, there was obtained an oily non-crystallineproduct identified as 17a-ethinyl-3-(pentane-3-sulfonyloxy)- 1713hydroxy 1,3,5(10) estratriene. [a] +4.2 (CHCl 11 3620, 3320, 1615, 1590,1500, 1370, 1185 cm.- (CHCl EXAMPLE 20 17u-ethiny1-3-(3-methylbutane-1-sulfonyloxy)-17phydroxy-1,3,5'(10)-estratriene EXAMPLE 21 17a-ethinyl-B- (cyclopentanesulf0nyloxy)-17phydroxy-1,3,5 10) -estratrieneThe process was again the same as in Example 1 except for the startingproducts. From 1 g. of17a-ethinyl-3-hydroxy-17fl-trimethylsilyloxy-1,3,5(10)-estratriene, 28ml. of a mixture of benzene and triethylamine, and 1.73 ml.

cyclopentane-sulfonylchloride, there was obtained a crystalline productidentified as 17a-ethinyl-3-(cyclopentane sulfonyloxy) 17phydroxy-1,3,5(10)-estratriene. M.P. 162-164 C.; [01], +13.9 (CHCI v3615, 3315, 1610, 1590, 1505, 1385, 1180 cm.- (CHCIg).

7 EXAMPLE 22 l 7a-ethinyl-3- (cyclopentanesulfonyloxy 17 pacctoxy-1,3,5estratriene The process was the same as in Example 1. The startingproducts were 0.92 g. of 17u-ethinyl-3-hydroxy-17 8-acetoxy-1,3,5(10)-estratriene, 28 ml. of a mixture of benzene andtriethylamine and 1.73 ml. cyclopentanesulfonylchloride. There wasobtained a crystalline 17aethinyl-3- (cyclopentanesulfonyloxy)17/3-acet0xy-1,3,5(10)-estratriene. M.P. 151-153 C.; [a] Z (CHCl 113320, 1750, 1615, 1590, 1500, 1375, 1275, 1180 cmr (CHCl EXAMPLE 2317a-ethiny1-3-(cyclopentanesulfonyloxy)-175- valerianoxy-1,3,5 10)estratriene The process was the same as in Example 1. The startingproducts were 1.035 g. of 17a ethinyl-3-hydroxy-17B-valerianoxy-1,3,5(10)-estratriene, 28 ml. of a mixture of benzene andtriethylamine and 1.73 ml. cyclopentanesulfonylchloride. There wasobtained 17a-ethinyl-3-cyc1opentanesulfonyl) 17B valerianoxyl,3,5(10)-estratriene. [a] +11.3 (CHCl u 3320, 1755, 1615, 1590, 1500,1375, 1185 cm.- (CHC1 EXAMPLE 24 17a-ch1oroethinyl-3-(cyclopentanesulfonyloxy 175- hydroxyl ,3,5( 10) estratriene The processwas the same as in Example 1. The starting products were 1.09 g. of17u-chloroethinyl-3hydroxyl7 3-trimethylsilyloxy-L3,5(10)-estratriene,28 ml. of a mixture of benzene and 2,6-dimethylpyridine and 1.7 3 ml.cyclopentanesulfonylehloride. There was obtained 17achloroethinyl 3(cyclopentanesulfonyloxy) 17fl-hydroxy-1,3,5(10)-estratriene. v 3620,2230, 1615, 1590, 1500, 1375, 1180 cm. (CHCl EXAMPLE 2517a-ethinyl-3-(cyclohexanesulfonyloxy)-17fl-hydroxy- 1,3 ,5 10estratriene The process was the same as in Example 1. The startingproducts were 1 g. of17a-ethinyl-3-hydroxy-17fi-trimethylsilyloxy-1,3,5(10)-estratriene, 28ml. of a mixture of benzene and triisopropylamine and 2.02 ml.cyclohexanesulfonylbromide. There was obtained an oily non-crystalline17a-ethinyl-3-(cyclohexanesulfonyloxy)-17fi-hydroxy-1,3,5(10)-estratriene. [a] 2 +5.5 (CHC1 u 3620', 3320, 1610, 1500, 1375,1180 emf- (CHCl EXAMPLE 26 17a-ethinyl-3- (tolueneu-sulfonyloxy)17,6-hydroxy- 1,3,5 10) estratriene EXAMPLE 27l7a-ethinyl-3-(diethylamino-sulfonyloxy)-1713-hydroxy-1,3,5(10)-estratriene The process was the same as in Example 1.The starting products were 1 g. of 17-ethinyl-3-hydroxy-l7fl-trimethylsilyloxyl,3,5(10)-estratriene, 28 ml.of a mixture of benzene and triethylamine and 1.90 ml.diethylaminosulfonylchloride. There was obtained a crystalline productwhich was 17a-ethinyl-3-(diethylamino-sulfonyloxy)17/3- hydroxy-1,3,5(10)-estratriene. M.P. 113-116 C.; [111 8 +13.8 (CHCl v 3620, 3320,1615, 1590, 1500, 1380, 1180 cm. (CHCl EXAMPLE 2817ot-ethinyl-3-(pyrrolidino-sulfonyloxy)-1713- hydroxy-1,3,5 10)estratriene The process was the same as in Example 1. The startingproducts were 1 g. of17u-ethinyl-3-hydroxy-17,6-trimethylsilyloxy-1,3,5(10)-estratriene, 28ml. of a mixture of benzene and collidine and 1.66 ml. ofpyrrolidinosulfonylchloride. There was obtained a crystalline productwhich was 17u-ethinyl 3 (pyrrolidinosulfonyloxy)-l7;3-hydroxy-1,3,5(10)-estratriene, M.P. 116-122" C.; [a]+10.5 (CHCl v 3620, 3320, 1615, 1590, 1500, 1385, 1180 cm.- (CHClEXAMPLE 29 17 a-ethinyl-3- piperidino-sulfonyloxy) hydroxy-1,3,510)-estratriene The process was the same as in Example 1. The startingproducts were 1 g. of17a-ethiny1-3-hydroxy-17,3-trimethylsilyloxy-1,3,5(10)-estratriene, 28ml. of a mixture of benzene and triethylamine and 1.95 ml. ofpiperidinosulfonyl chloride. There was obtained a crystalline productwhich was 17 a-ethinyl-3-( piperidino-sulfonyloxy)-1718-hydroxy-l,3,5(10)-estratriene, M.P. 1'03109 C.; [a] 4.25 (CHC 3); I3615, 3320', 1615, 1590, 1500, 1385, 1195 cm. (CHCl What is claimed is:

1. A compound of the formula ---CECH 2. A compound according to claim 1designated 17ozethinyl 3 (propane 2 sulfonyloxy)-1713-hydroxy-1,3,5 1-0estratriene.

3. A compound according to claim 1 designated 17aethinyl 3 (butane 1sulfonyloxy)-17,6-hydroxy-1,3,5 10)-estratriene.

4. A compound according to claim 1 designated 17ozethiny1-3-(octane 1sulfonyloxy) 17,8 hydroxy-1,3, 5 10) estratriene.

5. A compound according to claim 1 designated 17aethinyl-3-(ethane 1sulfonyloxy)17fl-hydroxy 1,3,5 1-0 estratriene.

6. A compound according to claim 1 designated 17ccethinyl 3(propane-l-sulfonyloxy)-17fl-hydroxy 1,3,5 10) estratriene.

7. 17a-ethinyl 3 (propane 2 sulfonyloxy) 17 3- acetoxy-1,3,510)-estratriene.

CHz-CH:

8. 17a-ethiny1 3 (propane 2 sulfonyloxy) 17fivalerianoxy-1,3,5 10)-estratriene.

9. A compound according to claim 1 designated 17aethinyl 3(butane-Z-sulfonyloxy) 17,3 hydroxy-1,3, 5( -estratriene.

10. A compound according to claim 1 designated 17ozethinyl 3(Z-methyl-propane 1 sulfonyloxy) 17B- hydroxy-1,3,5 10) -estratriene.

11. A compound according to claim 1 designated 17ozethinyl 3 (pentane 1sulfonyloxy) 17p hydroxy- 1,3,5 10)-estratriene.

12. A compound according to claim 1 designated 17aethinyl 3 (pentane 3sulfonyloxy) 175 hydroxy- 1,3,5 [10)-estratriene.

13. A compound according to claim 1 designated 17aethinyl 3(B-methyl-butane 1 sulfonyl)-17fi-hydroxy- 1,3,5 10)-estratriene.

14. A compound according to claim 1 designated 17aethinyl 3(cyclopentane-sulfonyloxy) 17,8 hydroxy- 1,3,5 (10)-estratriene.

15. 17a ethinyl 3 (cyclopentane-sulfonyloxy) 17B- acetoxy-1,3,5 10)-estratriene.

16. 17a-ethinyl 3 (cyclopentane-sulfonyloxy) 17pvalerianoxy-1,3,5( 10)-estratriene. I

17. A compound according to claim 1 designated 17aethinyl 3(cyclohexane-sulfonyloxy)-17;3-hydr0xy-1,3, 5 10 -estratriene.

18. A compound according to claim 1 designated 17aethinyl 3(toluene-a-sulfonyloxy) 17p hydroxy-1,3, 5 (10)-estratriene.

19. A compound according to claim 1 designated 17aethinyl 3(diethylamino-sulfonyloxy) 17p hydroxy- 1,3,5(10)-estratriene.

20. A compound according to claim 1 designated 17aethinyl 3(pyrrolidino-sulfonyloxy)-17fl-hydroxy-1,3,5 10) -estratriene.

21. A compound according to claim 1 designated 17aethinyl 3(piperidino-sulfonyloxy) 17p hydroxy- 1,3,5 10 -estratriene.

References Cited UNITED STATES PATENTS 3,522,281 7/1970 Anner et a1260-3975 3,580,937 5/1971 Allen et al 260397.4

FOREIGN PATENTS 996,309 Great Britain 260-3975 OTHER REFERENCES Fieseret al.: Steroids (1959), p. 476 relied on. Chem. Abstracts, vol. 52(1968), par. 17.627b.

ELBERT L. ROBERTS, Primary Examiner US. Cl. X.R.

